Anticancer Activity and Molecular Docking Analysis of Trans-Cinnamic Acid in Human Lung Cancer

Lung cancer is known to have a very high incidence and mortality rate. Trans-cinnamic acid (tCA) is a phenolic compound found in various fruits and vegetables and is known to have many effects such as antimicrobial, anti-inflammatory and anticancer. In this study, molecular docking analysis was performed to predict the binding affinities of tCA toward apoptosis- and ER stress-related target proteins. The effects of tCA on proliferation, apoptosis and endoplasmic reticulum (ER) stress gene expression, colony forming ability, total antioxidant status (TAS) and total oxidant status (TOS) in A549 human lung cancer cells were investigated. Cell proliferation and, expression levels of genes associated with apoptosis and ER stress determined using XTT and qRT-PCR, respectively. ELISA test was used for TAS, TOS and caspase-3 levels. Molecular docking analysis predicted favorable binding affinities of tCA toward the investigated target proteins. The IC₅₀ value of tCA in A549 cells was found to be 2.59 mM at 48 h. Treatment with tCA significantly increased the expression of apoptosis genes including BAX, CASP3, CASP7, CASP8, CASP9, CYCS, and FADD. Among the ER stress-associated genes analyzed, only PERK and CHOP showed significant upregulation following tCA treatment, while no significant changes were observed in the remaining ER stress-related genes. Furthermore, tCA treatment caused a decrease in TAS level but an increase in TOS level. tCA suppressed the ability to form colonies in A549 cells according to the colony assay. In conclusion, tCA inhibited proliferation and colony formation, modulated selected apoptosis- and ER stress-related genes, and altered oxidative stress parameters in A549 cells. These in vitro findings provide preliminary evidence supporting the potential anticancer activity of tCA; however, further protein-level, functional, and in vivo studies are required to confirm the underlying mechanisms and therapeutic potential. The image outlines a study evaluating the anticancer effects of trans-cinnamic acid (tCA) on A549 lung cancer cells. Molecular docking analysis showed tCA has potential binding affinity to target proteins. In cell experiments, the IC50 of tCA was 2.59 mM at 48 h, determined by an XTT test. Treatment with tCA reduced TAS and caspase-3 levels while increasing TOS. RNA isolation and cDNA synthesis were followed by quantitative RT-PCR analysis, indicating that tCA may induce upregulation of ER stress and apoptotic markers in A549 cells. A colony assay demonstrated that tCA suppressed colony formation in these cells. ELISA assays for TAS, TOS, and caspase-3 were also performed as part of the analysis.